This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Septins are highly conserved, cytoskeletal proteins found in most eukaryotes including humans. They form filaments at the point of cell division and have a central role in cell cycle regulation, cell morphogenesis, and cancer. However, detailed understanding of septin function is lacking, partially due to the paucity of structural information. We are studying the structure of the yeast septin core complex and filaments by a variety of methods including electron microscopy, x-ray crystallography, and x-ray solution scattering. The complex is believed to be a 380 kD hetero-octamer in solution, composed of pairs of cdc3, cdc10, cdc11, and cdc12. We have grown crystals of the septin complex that diffract to low resolution (12 [unreadable]). We will improve the diffraction resolution by crystallizing different protein constructs. We will grow crystals of selenomethionine substituted protein to solve the structure by MAD phasing. We will also use isomorphous replacement with heavy atom soaked crystals to determine phases. Structural studies will reveal how septins form filaments and how filaments interact with other proteins involved in cell division. High resolution crystal structures will also facilitate the development of septin-targeted drugs that may be useful against cancer.